The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.

IF 2.7 4区医学 Q1 ORTHOPEDICS CARTILAGE Pub Date : 2024-03-19 DOI:10.1177/19476035241233659

Ellen G J Ripmeester, Jessica S J J Steijns, Karolina A P Wijnands, Roderick H M J Stassen, Vasek Pitelka, Laura C W Peeters, Andy Cremers, Nzekui M S A Astryde, Alzbeta Chabronova, Don A M Surtel, Pieter J Emans, Guus G H van den Akker, Bert van Rietbergen, Lodewijk W van Rhijn, Marjolein M J Caron, Tim J M Welting

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Abstract

Objective: Osteoarthritis (OA) is characterized by articular cartilage erosion, pathological subchondral bone changes, and signs of synovial inflammation and pain. We previously identified p[63-82], a bone morphogenetic protein 7 (BMP7)-derived bioactive peptide that attenuates structural cartilage degeneration in the rat medial meniscal tear-model for posttraumatic OA. This study aimed to evaluate the cartilage erosion-attenuating activity of p[63-82] in a different preclinical model for OA (anterior cruciate ligament transection-partial medial meniscectomy [anterior cruciate ligament transection (ACLT)-pMMx]). The disease-modifying action of the p[63-82] was followed-up in this model for 5 and 10 weeks.

Design: Skeletally mature male Lewis rats underwent ACLT-pMMx surgery. Rats received weekly intra-articular injections with either saline or 500 ng p[63-82]. Five and 10 weeks postsurgery, rats were sacrificed, and subchondral bone characteristics were determined using microcomputed tomography (µCT). Histopathological evaluation of cartilage degradation and Osteoarthritis Research Society International (OARSI)-scoring was performed following Safranin-O/Fast Green staining. Pain-related behavior was measured by incapacitance testing and footprint analysis.

Results: Histopathological evaluation at 5 and 10 weeks postsurgery showed reduced cartilage degeneration and a significantly reduced OARSI score, whereas no significant changes in subchondral bone characteristics were found in the p[63-82]-treated rats compared to the saline-treated rats. ACLT-pMMx-induced imbalance of static weightbearing capacity in the p[63-82] group was significantly improved compared to the saline-treated rats at weeks 5 postsurgery. Footprint analysis scores in the p[63-82]-treated rats demonstrated improvement at week 10 postsurgery.

Conclusions: Weekly intra-articular injections of p[63-82] in the rat ACLT-pMMx posttraumatic OA model resulted in reduced degenerative cartilage changes and induced functional improvement in static weightbearing capacity during follow-up.

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BMP7衍生肽p[63-82]可减少大鼠ACLT-pMMx创伤后骨关节炎模型中的软骨退化。

目的：骨关节炎（OA）的特征是关节软骨侵蚀、软骨下骨病理性改变以及滑膜炎症和疼痛。我们之前发现了一种骨形态发生蛋白 7（BMP7）衍生的生物活性肽 p[63-82]，它能减轻大鼠内侧半月板撕裂模型中创伤后 OA 的软骨结构退化。本研究旨在评估 p[63-82] 在不同的 OA 临床前模型（前交叉韧带横断-部分内侧半月板切除术 [前交叉韧带横断（ACLT）-pMMx]）中的软骨侵蚀抑制活性。在该模型中，对 p[63-82] 的疾病调节作用进行了 5 周和 10 周的跟踪研究：设计：骨骼发育成熟的雄性 Lewis 大鼠接受 ACLT-pMMx 手术。大鼠每周接受生理盐水或 500 ng p[63-82] 关节内注射。手术后 5 周和 10 周，大鼠被处死，并使用微计算机断层扫描（µCT）确定软骨下骨的特征。软骨退化的组织病理学评估和国际骨关节炎研究学会（OARSI）评分是在 Safranin-O/Fast Green 染色后进行的。与疼痛相关的行为通过失能测试和足迹分析进行测量：结果：术后5周和10周的组织病理学评估显示，p[63-82]处理的大鼠软骨退化程度降低，OARSI评分显著降低，而软骨下骨特征与生理盐水处理的大鼠相比没有发生显著变化。在术后第 5 周，p[63-82]组大鼠的 ACLT-pMMx 引起的静态负重能力不平衡与生理盐水治疗组相比有明显改善。p[63-82]治疗组大鼠的足印分析评分在术后第10周有所改善：结论：在大鼠 ACLT-pMMx 创伤后 OA 模型中，每周关节内注射 p[63-82] 可减少软骨退行性变化，并在随访期间改善静态负重能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CARTILAGE ORTHOPEDICS-

CiteScore

6.90

自引率

7.10%

发文量

期刊介绍： CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.